A5076452380- Immune Cell Function and Interaction
- Reproductive System and Pregnancy
- Medical and Agricultural Research Studies
- Migration, Aging, and Tourism Studies
- Climate Change, Adaptation, Migration
- Viral-associated cancers and disorders
- Autoimmune Neurological Disorders and Treatments
- Immunodeficiency and Autoimmune Disorders
- Systemic Lupus Erythematosus Research
- Multiple Sclerosis Research Studies
- Pregnancy and preeclampsia studies
- IL-33, ST2, and ILC Pathways
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- interferon and immune responses
- Polyomavirus and related diseases
- Epigenetics and DNA Methylation
- RNA regulation and disease
- Peripheral Neuropathies and Disorders
- Birth, Development, and Health
- Neuroinflammation and Neurodegeneration Mechanisms
- Systemic Sclerosis and Related Diseases
- Atherosclerosis and Cardiovascular Diseases
- SARS-CoV-2 and COVID-19 Research
- Cell death mechanisms and regulation
Westmead Institute for Medical Research
2016-2024
The University of Sydney
2015-2024
Westmead Institute
2015-2022
Westmead Hospital
2009-2019
Royal College of Pathologists of Australasia
2018
Inositol pyrophosphates (PP-IPs) comprising inositol, phosphate, and pyrophosphate (PP) are essential for multiple functions in eukaryotes. Their role fungal pathogens has never been addressed. Cryptococcus neoformans is a model pathogenic fungus causing life-threatening meningoencephalitis. We investigate the cryptococcal kinases responsible production of PP-IPs (IP7/IP8) hierarchy PP-IP importance pathogenicity. Using gene deletion inositol polyphosphate profiling, we identified Kcs1 as...
Objective Vaccination against hepatitis B virus (HBV) confers protection from subsequent infection through immunological memory that is traditionally considered the domain of adaptive immune system. This view has been challenged following identification antigen-specific natural killer cells (mNKs) in mice and non-human primates. While presence mNKs suggested humans based on expansion NK pathogen exposure, evidence regarding antigen-specificity lacking. Here, we demonstrate existence...
Genome wide association studies have identified > 200 susceptibility loci accounting for much of the heritability multiple sclerosis (MS). Epstein-Barr virus (EBV), a memory B cell tropic virus, has been as necessary but not sufficient development MS. The molecular and immunological basis this established. Infected proliferation is driven by signalling through EBV produced surface protein LMP1, homologue MS risk gene CD40. We investigated transcriptomes cells EBV-infected at Latency III...
Although the causes of Multiple Sclerosis (MS) still remain largely unknown, multiple lines evidence suggest that Epstein–Barr virus (EBV) infection may contribute to development MS. Here, we aimed identify potential contribution EBV-encoded and host cellular miRNAs MS pathogenesis. We identified differentially expressed in EBV infected B cells (LCLs) putative host/EBV miRNA interactions with risk loci. estimated genotype effect loci on miRNA:mRNA silico. found protective allele SNP...
Summary Common variable immunodeficiency (CVID) is a B cell disorder characterized frequently by failure of memory development and antibody secretion. A unifying cellular pathogenesis for CVID has not been forthcoming, but given the immunoregulatory role invariant NK (iNK) T cells their absence in several other immunodeficiencies, we quantified these blood 58 patients. There was marked decrease proportion iNK patients compared with controls. This particularly notable those low...
To investigate the molecular mechanisms through which Epstein-Barr virus (EBV) may contribute to Systemic Lupus Erythematosus (SLE) pathogenesis, we interrogated SLE genetic risk loci for signatures of EBV infection. We first compared gene expression profile genes across 459 different cell/tissue types. EBV-infected B cells (LCLs) had strongest representation highly expressed genes. By determining an allele effect on (expression quantitative trait loci, eQTL) in LCLs and 16 other immune cell...
Background: Autoimmune encephalitis (AE) is an important cause of refractory epilepsy, rapidly progressive cognitive decline and unexplained movement disorders in adults. Whilst there identification increasing number associated autoantibodies, patients remain with a high clinical probability autoimmune but no characterised autoantibody. These represent diagnostic treatment dilemma. Objective: To evaluate routine novel tests cerebrospinal fluid (CSF) AE to attempt identify better biomarkers...
Multiple Sclerosis (MS) is a complex immune-mediated disease of the central nervous system. Treatment based on immunomodulation, including specifically targeting B cells. cells are main host for Epstein-Barr Virus (EBV), which has been described as necessary MS development. Over 200 genetic loci have identified increasing susceptibility to MS. Many risk genes altered expression in EBV infected cells, dependent genotype, and themselves regulated by transcription factor EBNA2. Females 2-3...
Monocytes are likely to play a significant role in the pathogenesis of preeclampsia (PE) and intrauterine fetal growth restriction (IUGR), given their homeostasis tissue repair. Our aim was study gestational changes monocytes normal pregnancy determine whether monocyte subsets phenotype altered complications, such as PE IUGR.A prospective cross-sectional case-control conducted. Pregnant women between 24 40 weeks gestation (n = 54) were recruited classified into four clinical groups...
Abstract Background The mechanisms linking UV radiation and vitamin D exposure to the risk of acquiring latitude critical period-dependent autoimmune disease, multiple sclerosis, is unclear. We examined effect on DNA methylation at receptor binding sites in adult paediatric myeloid cells. This was accomplished through differentiating CD34+ haematopoietic progenitors into CD14+ mononuclear phagocytes, presence absence calcitriol. Results Few changes occurred cells treated with However,...
We developed a 25-color flow cytometry panel to comprehensively interrogate innate lymphoid cells (ILC), mucosal-associated invariant T (MAIT) cells, natural killer (NK) and γδ in human tissues. The ability isolate these from fresh tissue is crucial understanding the role play at immune-privileged mucosal surfaces like intestine health disease settings. However, liberating extremely challenging as many key surface identification markers are susceptible enzymatic cleavage. Choosing correct...
Abstract Background There is little available data on fetal monocyte phenotype and function. A prospective cross-sectional pilot study was conducted to describe the cord blood subset in preeclampsia (PE) growth restriction (FGR) as compared normal pregnancy maternal circulation. Methods Maternal samples from 27 pregnancies were collected at delivery pregnancy, PE, FGR PE+FGR. The distribution of subtypes characterized by CD14 CD16 expression using flow cytometry for each clinical group a...
Epidemiological, molecular and genetic studies have indicated that high serum vitamin D levels are associated with lower risk of several autoimmune diseases. The receptor (VDR) binding sites in monocytes dendritic cells (DCs) more common genes for diseases latitude dependence than other transcription factor Zinc finger MIZ domain-containing protein 1 (ZMIZ1) interferon regulatory 8 (IRF8)-risk many these diseases-have VDR peaks co-incident the single nucleotide polymorphisms (SNPs). We show...
The data presented in this article are related to the research entitled "The autoimmune risk gene ZMIZ1 is a vitamin D responsived marker of molecular phenotype multiple sclerosis" Fewings et al. (2017) [1]. Here we identify set genes correlated with cohorts, provide phenotypic details on those and negatively cells predominantly expressing genes. We metabolic pathways which over-represented. Finally, present flow cytometry gating strategy have used immune from blood producing RPS6.
Sepsis is associated with a dysregulated inflammatory response to infection. Despite the activation of inflammation, an immune suppression often observed, predisposing patients secondary infections. Therapies directed at restoration immunity may be considered but should guided by status patients. In this paper, we described use high-dimensional flow cytometry (HDCyto) panel assess immunophenotype sepsis. We then isolated peripheral blood mononuclear cells (PBMCs) from septic shock and...
Circulating levels of the anti-angiogenic factors sFlt-1 and sEndoglin are elevated in preeclampsia (PE) fetal growth restriction (FGR), mainly secreted from placental trophoblast. This study aims to identify contributory role monocyte Flt-1 endoglin expression PE FGR.
Abstract Background The mechanisms linking UV radiation and vitamin D exposure to the risk of acquiring latitude critical period dependent autoimmune disease, multiple sclerosis, is unclear. We examined effect on DNA methylation as well at receptor binding sites in adult paediatric myeloid cells. Results Very few changes occurred cells treated with calcitriol. However, several VDR across genome demonstrated increased origin. Genes associated these were enriched for intracellular signalling...
A promising new avenue of MS research that may lead to a better understanding pathogenesis, progression and therapeutic response, development therapies, comes from the recent identification defined immune cell populations are highly heritable. Such stable have been identified in three papers using extensive flow cytometric panels investigate twin family cohorts. They showed while most variation between individuals was not heritable, some was. This heritability sometimes very high, authors...